Insulin Delivery Technology for Treatment of Infants with Neonatal Diabetes Mellitus: A Systematic Review.

Neonatal diabetes mellitus is a rare disorder of glucose metabolism with onset within the first 6 months of life. The initial treatment is based on insulin infusion. The technologies for diabetes treatment can be very helpful, even if guidelines are still lacking. The current study aimed to provide a comprehensive review of the literature about the safety and efficacy of insulin treatment with technology for diabetes to support clinicians in the management of infants with neonatal diabetes mellitus. A total of 22 papers were included, most of them case reports or case series. The first infants with neonatal diabetes mellitus treated with insulin pumps were described nearly two decades ago. Over the years, continuous glucose monitoring systems were added to treat these individuals, allowing for a better customization of insulin administration. Insulin was diluted in some cases to further minimize the doses. Improvement in technology for diabetes prompted clinicians to use new devices and algorithms for insulin delivery in infants with neonatal diabetes as well. These systems are safe and effective, may shorten hospital stay, and help clinicians weaning insulin during the remission phase in the transient forms or switching from insulin to sulfonylurea when suggested by the molecular diagnosis. New technologies for insulin delivery in infants with neonatal diabetes can be used safely and closed-loop algorithms can work properly in these situations, optimizing blood glucose control.

Women's and Partners' Experiences With a Closed-loop Insulin Delivery System to Manage Type 1 Diabetes in the Postpartum Period.

OBJECTIVES: Closed-loop insulin delivery has the potential to offer women with type 1 diabetes a break from intense diabetes self-care efforts postpartum. Our aim in this study was to explore the views and opinions of hybrid closed-loop users and their partners in the first 24 weeks postpartum. METHODS: This qualitative study was embedded in a controlled study of women with type 1 diabetes randomized to closed-loop insulin delivery (MiniMed™ 670G or 770G) or sensor-augmented pump use for 1 to 11 weeks 6 days postpartum, with all on closed-loop delivery from 12 to 24 weeks postpartum. Semistructured interviews were conducted with 16 study participants and their partners at 12 and 24 weeks postpartum. Thematic analyses were used to examine participants' and partners' experiences. RESULTS: Participants' positive perceptions of closed-loop use related to reduced hypoglycemia, in contrast to previous experiences with nonautomated insulin delivery. These perceptions were balanced against frustrations with the system, allowing blood glucose levels to be higher than desired. Closed-loop use did not influence infant feeding choice, but infant feeding and care impacted participants' diabetes management. Partners expressed uncertainty about the closed loop taking away control from participants who were highly skilled with diabetes self-management. CONCLUSIONS: Participants reported that closed-loop insulin delivery resulted in less time spent in hypoglycemia when compared with the previously used nonautomated delivery. Yet, participants desired a greater understanding of the workings of the closed-loop algorithm. Our study provides potential users with realistic expectations about the experience with the MiniMed 670G or 770G closed-loop system in the postpartum period.

Efficacy and Safety of Different Hybrid Closed Loop Systems for Automated Insulin Delivery in People With Type 1 Diabetes: A Systematic Review and Network Meta-Analysis.

AIMS: To compare the efficacy and safety of different hybrid closed loop (HCL) systems in people with diabetes through a network meta-analysis. METHODS: We searched MEDLINE, EMBASE, CENTRAL and PubMed for randomised clinical trials (RCTs) enrolling children, adolescents and/or adults with type 1 or type 2 diabetes, evaluating Minimed 670G, Minimed 780G, Control-IQ, CamAPS Fx, DBLG-1, DBLHU, and Omnipod 5 HCL systems against other types of insulin therapy, and reporting time in target range (TIR) as outcome. RESULTS: A total of 28 RCTs, all enrolling people with type 1 diabetes, were included. HCL systems significantly increased TIR compared with subcutaneous insulin therapy without continuous glucose monitoring (SIT). Minimed 780G achieved the highest TIR ahead of Control IQ (mean difference (MD) 5.1%, 95% confidence interval (95% CI) [0.68; 9.52], low certainty), Minimed 670G (MD 7.48%, 95% CI [4.27; 10.7], moderate certainty), CamAPS Fx (MD 8.94%, 95% CI [4.35; 13.54], low certainty), and DBLG1 (MD 10.69%, 95% CI [5.73; 15.65], low certainty). All HCL systems decreased time below target range, with DBLG1 (MD -3.69%, 95% CI [-5.2; -2.19], high certainty), Minimed 670G (MD -2.9%, 95% CI [-3.77; -2.04], moderate certainty) and Minimed 780G (MD -2.79%, 95% CI [-3.94; -1.64], high certainty) exhibiting the largest reductions compared to SIT. The risk of severe hypoglycaemia and diabetic ketoacidosis was similar to other types of insulin therapy. CONCLUSIONS: We show a hierarchy of efficacy among the different HCL systems in people with type 1 diabetes, thus providing support to clinical decision-making. TRIAL REGISTRATION: PROSPERO CRD42023453717.

Performance of the MiniMed 780G system on mitigating menstrual cycle-dependent glycaemic variability.

AIM: To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle. MATERIALS AND METHODS: A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed-loop (AHCL) period; each period lasted 3 consecutive months. RESULTS: During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P < .01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P < .01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P = .72), without increasing the time spent below 70 mg/dL (P > .05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P < .01), during the luteal phase. CONCLUSIONS: The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle-dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle.

12-Month Time in Tight Range Improvement with Advanced Hybrid-Closed Loop System in Adults with Type 1 Diabetes.

INTRODUCTION: Time in tight range (TITR) is an emerging and valuable metric for assessing normoglycemia. The latest advancement in automated insulin delivery (AID) systems, the advanced hybrid closed-loop (AHCL) systems, are particularly noteworthy for managing type 1 diabetes (T1D) and enhancing glycemic control. METHODS: In a real-world clinical setting, we carried out a retrospective evaluation of TITR in 42 adult subjects with T1D using the AHCL Minimed™ 780G system over a 12-month period. RESULTS: Within just 14 days of activating the automatic mode, the AHCL Minimed™ 780G system showed rapid improvement in TITR, and in the other continuous glucose monitoring (CGM) metrics. This improvement persisted over 12 months, achieving the proposed 45-50% range for effective glycemic control. CONCLUSION: The AHCL Minimed™ 780G system significantly enhances TITR, demonstrating continuous improvement throughout a 12-month follow-up period.

Applying technologies to simplify strategies for exercise in type 1 diabetes.

Challenges and fears related to managing glucose levels around planned and spontaneous exercise affect outcomes and quality of life in people living with type 1 diabetes. Advances in technology, including continuous glucose monitoring, open-loop insulin pump therapy and hybrid closed-loop (HCL) systems for exercise management in type 1 diabetes, address some of these challenges. In this review, three research or clinical experts, each living with type 1 diabetes, leverage published literature and clinical and personal experiences to translate research findings into simplified, patient-centred strategies. With an understanding of limitations in insulin pharmacokinetics, variable intra-individual responses to aerobic and anaerobic exercise, and the features of the technologies, six steps are proposed to guide clinicians in efficiently communicating simplified actions more effectively to individuals with type 1 diabetes. Fundamentally, the six steps centre on two aspects. First, regardless of insulin therapy type, and especially needed for spontaneous exercise, we provide an estimate of glucose disposal into active muscle meant to be consumed as extra carbohydrates for exercise ('ExCarbs'; a common example is 0.5 g/kg body mass per hour for adults and 1.0 g/kg body mass per hour for youth). Second, for planned exercise using open-loop pump therapy or HCL systems, we additionally recommend pre-emptive basal insulin reduction or using HCL exercise modes initiated 90 min (1-2 h) before the start of exercise until the end of exercise. Modifications for aerobic- and anaerobic-type exercise are discussed. The burden of pre-emptive basal insulin reductions and consumption of ExCarbs are the limitations of HCL systems, which may be overcome by future innovations but are unquestionably required for currently available systems.

Safety of Options to "Boost" (Enhancing Insulin Infusion Rates) and "Ease-Off" (Reducing Insulin Infusion Rates) in CamAPS FX Hybrid Closed-Loop System: A Real-World Analysis.

The usage and safety of the Boost and Ease-off features in the CamAPS FX hybrid closed-loop system were analyzed in a retrospective analysis of real-world data from 7,464 users over a 12-month period. Boost was used more frequently than Ease-off, but for a shorter duration per use. Mean starting glucose was above range for Boost (229 ± 51 mg/dL), and within range for Ease-off (114 ± 29 mg/dL). Time spent below 70 mg/dL was low during Boost periods [median (interquartile range; IQR) 0.0% (0.0, 0.5%)], and lower than during no Boost periods [2.1% (1.2, 3.4%)], while time spent above 180 mg/dL was lower during Ease-off periods (15 ± 14%) compared with no Ease-off periods (25 ± 12%). There were no episodes of severe hypoglycemia or diabetic ketoacidosis attributed to Boost or Ease-off use. Boost and Ease-off allow users to engage safely with CamAPS FX to manage their glucose levels during periods of more-than-usual and less-than-usual insulin needs.

Systematic review of disparities in continuous glucose monitoring and insulin pump utilization in the United States: Key themes and evidentiary gaps.

AIM: This study aims to provide a comprehensive overview of real-world evidence pertaining to disparities in the utilization of continuous glucose monitors (CGMs)/insulin pumps to highlight potential evidentiary gaps and discern emerging themes from the literature. MATERIALS AND METHODS: A systematic review of published manuscripts and abstracts was conducted from: MEDLINE, EMBASE, Nursing and Allied Health, Web of Science and CINHAL. Attributes related to patients, outcomes, interventions (CGMs/pumps/both) and study type were captured. In addition, factors associated with disparities in device utilization were examined. RESULTS: Thirty-six studies were included in the final analysis; the studies predominantly focused on people living with type 1 diabetes. Only two studies included individuals with type 2 diabetes. Almost two-thirds of the studies reported outcomes associated with disparities (e.g. glycated haemoglobin, diabetic ketoacidosis, resource utilization). Most studies highlighted disparities across race, ethnicity and insurance type. Evidentiary gaps were identified, particularly in the evidence for people with type 2 diabetes, the continuation of CGM/pump use and limited studies addressing disparities among Native Americans/American Indians. CONCLUSION: This study reveals critical disparities in diabetes technology use across race, ethnicity and insurance type, particularly among people with type 1 diabetes. Evidentiary gaps assessing disparities in diabetes technology use persist, particularly concerning people with type 2 diabetes, Native American/American Indian and LGBTQ+ populations, and in outcomes related to continuation of use. Social and digital determinants of health, such as income, transportation, residential location and technological literacy, are crucial to achieving equitable access. Future research should focus on the patient journey to identify opportunities for equitable access to diabetes technology as its use grows.

Managing blood glucose levels with a hybrid closed-loop system in a patient with type 1 diabetes mellitus on enteral nutrition: A case report.

The achievement of glycemic management is challenging in patients with diabetes on enteral nutrition, limited literature exists on hybrid closed-loop systems' efficacy in such a situation. We described the case of a patient with type 1 diabetes treated by advanced hybrid closed loop on enteral nutrition with satisfactory glycemic management.

Impact on Glycemia Risk Index and other metrics in type 1 adult patients switching to Advanced Hybrid Closed-Loop systems: a one-year real-life experience.

BACKGROUND: Advanced Hybrid Closed-Loop system (AHCL) has profoundly changed type 1 diabetes therapy. This study primarily aimed to assess the impact on Glycemia Risk Index (GRI) and other continuous glucose monitoring (CGM) metrics when switching from one of four insulin strategies to AHCL in type 1 adult patients. METHODS: A single-center, retrospective pre/post observational study; 198 patients (age 44.4 ± 12.7 years, 115 females/83 males, diabetes duration 24.7 ± 11.6 years, HbA1c 7.4 ± 1%), treated with different insulin therapies (MDI, CSII, SAP with PLGS, HCL) were assessed before and after switching to an AHCL (MiniMed 780G, Diabeloop Roche, Tandem Control-IQ) at 1, 3, 6, and 12 months. Mixed-effects multivariable regression models were used to estimate the mean pre/post variations at different time points, adjusted for potential confounders. RESULTS: A month after the switch, there was an improvement in CGM metrics and HbA1c for all patients: GRI -10.7, GMI -0.27%, CV -2.1%, TAR>250 -3.7%, TAR180-250 -5.6%, TIR + 9.7%, HbA1c -0.54% (all p < 0.001). This improvement was maintained throughout the observational period (at 3, 6, and 12 months, with all p-values < 0.001). When improvements across the 780, Diabeloop, and Tandem CIQ devices were compared: Diabeloop demonstrated significantly better performance in terms of GRI, GMI, CV, TAR>250 at T1 (for all p < 0.01); 780 recorded highest average decrease in TAR180-250 (p = 0.020), while Tandem achieved the most significant reduction in TBR54-69 (p = 0.004). CONCLUSIONS: Adopting an AHCL leads to a rapid and sustained improvement in GRI and other parameters of metabolic control for up to a year, regardless of prior insulin therapies, baseline conditions or brands.

Efficacy of advanced hybrid closed loop systems in cystic fibrosis related diabetes: a pilot study.

Background and aims: Cystic fibrosis related diabetes (CFRD) is correlated with worsening of nutritional status and greater deterioration of lung function. The role of new technologies for the treatment of CFRD is little explored. The aim of the study was to evaluate the efficacy of Advanced Hybrid Closed Loop (AHCL) systems on glycemic control in CF patients. Methods: A single-center retrospective study on CFRD patients using AHCL systems was performed. Glycated hemoglobin (HbA1c) values and Continuous Glucose Monitoring (CGM) metrics were collected at T0 (AHCL placement), T1 (1-month), T2 (6-months) and T3 (1-year) to evaluate glycemic control. Results: 10 patients were included in the study. Data showed a reduction of HbA1c value (7.31 ± 0.34 to 6.35 ± 1.00; p=0.03), glycemic variability (p=0.05) and insulin requirement (p=0.03). The study population reached American Diabetes Association (ADA) recommended glycemic targets at 1-year. An increase in the Time in Range (TIR) and a reduction in time in hyperglycemia were also observed, although not statistically significant. Conclusions: In patients with CFRD, the use of AHCL leads to an improvement in glycemic control in terms of HbA1c and glycemic variability. The increase in TIR and the reduction of time in hyperglycemia, although not statistically significant, are extremely encouraging from a clinical point of view. Further studies with a larger population and a longer follow-up are needed. The results of this study demonstrate the importance of proposing the use of AHCL even in CF patients, who could benefit from glycemic improvement also in terms of nutritional status and respiratory function.

Real-World Use of Hybrid Closed-Loop Systems during Diabetes Camp: A Preliminary Study for Secure Configuration Strategies in Children and Adolescents.

The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.

Offlabel use of Medtronic MiniMed 780G in the management of cystic fibrosis related diabetes in people requiring insulin total daily doses below 8 units: encouraging data from our population.

Cystic fibrosis (CF)-related diabetes (CFRD), characterized by partial to complete impaired insulin secretion, is the most common extra-pulmonary complication of CF. Actually, insulin is the only approved therapy for its management. Advanced hybrid closed loop (AHCL) systems are the gold standard therapy for type 1 diabetes and have been proposed for other insulin-dependent forms of diabetes, including CFRD. With AHCL systems, people with CFRD can better manage several typical disease-related issues, such as minimal insulin requirements, its variability due to exacerbations or concomitant steroid therapies, nutritional behaviors, the co-existence of CF complications as intestinal malabsorption or liver disease. SmartGuard, the AHCL system for Medtronic Minimed 780G, requires a minimum of 8 units per day to operate. In this paper, we expose a case of two young women with CFRD with total daily insulin requirements < 8 UI, using off-label SmartGuard system over a 3 years of follow-up period, suggesting an evaluation of its use also in people with minimal insulin needs, considering its beneficial impact in glucose control and quality of life.

Safety and Psychological Outcomes of Tandem t:Slim X2 Insulin Pump with Control-IQ Technology in Children, Adolescents, and Young Adults with Type 1 Diabetes: A Systematic Review.

The Tandem t:slim X2 insulin pump is a second-generation automated insulin delivery system with Control-IQ technology. It consists of an X2 insulin pump, an integrated Dexcom sensor, and an embedded 'Control-IQ' algorithm, which predicts glucose levels 30 min in the future, adapting the programmed basal insulin rates to get glucose levels between 112.5 and 160 mg/dl (8.9 mmol/l). The system delivers automatic correction boluses of insulin when glucose levels are predicted to rise > 180 mg/dl (10 mmol/l). It has been commercially available since 2016. We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults living with type 1 diabetes. We screened 552 papers, but only 21 manuscripts were included in this review. Fear of hypoglycemia is significantly reduced in young people with diabetes and their parents. Interestingly, diabetes-related distress is decreased; thus, the system is well accepted by the users. The sleeping quality of subjects living with diabetes and their caregivers is improved to a lesser extent as well. Despite the small number of data, this system is associated with a low rate of exercise-related hypoglycemia. Finally, evidence from the literature shows that this system is safe and effective in improving psychological personal outcomes. Even if further steps toward the fully closed loop are still mandatory, this second-generation automated insulin delivery system reduces the burden of diabetes. It properly addresses most psychological issues in children, adolescents, and young adults with type 1 diabetes mellitus; thus, it appears to be well accepted.

Retrospective observational study on real world use of the Minimed™ 780G automated insulin delivery system: Impact of the settings on autocorrection and omitted meal boluses.

INTRODUCTION: The Medtronic MiniMed™ 780G (MM780G) system uses an algorithm that includes autocorrection bolus (AB) delivery. This study evaluates the impact of omitted meal boluses and the system settings, glucose target and active insulin time (AIT), on the AB. METHOD: Retrospective observational study on data uploaded by all MiniMed 780G users in our healthcare area, obtained through the remote monitoring platform Care Connect, from April to August 2023. Downloads with a sensor usage time <95% were excluded. RESULTS: 235 downloads belonging to 235 users were analysed. AB delivery was significantly higher at 2 h AIT (36.08 ±â€¯13.17%) compared to the rest of settings (2.25-4 h) (26.43 ±â€¯13.2%) (p < 0.001). AB differences based on the glucose target were not found. Patients with <3 meal boluses per day had higher AB delivery (46.91 ±â€¯19.00% vs 27.53 ±â€¯11.54%) (p < 0.001) and had more unfavourable glucometric parameters (GMI 7.12 ±â€¯0.45%, TIR 67.46 ±â€¯12.89% vs GMI 6.78 ±â€¯0.3%, TIR 76.51 ±â€¯8.37%) (p < 0.001). However, the 2-h AIT group presented similar TAR, TIR and GMI regardless of the number of meal boluses. CONCLUSION: The fewer user-initiated boluses, the greater the autocorrection received. The active insulin time of 2 h entails a more active autocorrection pattern that makes it possible to more effectively compensate for the omission of meal boluses without increasing hypoglycaemias.

Postprandial Glucose Control With Different Hybrid Closed-Loop Systems According to Type of Meal in Adults With Type 1 Diabetes.

BACKGROUND: Hybrid Closed-Loop Systems (HCLs) may not perform optimally on postprandial glucose control. We evaluated how first-generation and advanced HCLs manage meals varying in carbohydrates, fat, and protein. METHOD: According to a cross-sectional design, seven-day food records and HCLs reports from 120 adults with type 1 diabetes (MiniMed670G: n = 40, MiniMed780G: n = 49, Control-IQ [C-IQ]: n = 31) were analyzed. Breakfasts (n = 570), lunches (n = 658), and dinners (n = 619) were divided according to the median of their carbohydrate (g)/fat (g) plus protein (g) ratio (C/FP). After breakfast (4-hour), lunch (6-hour), and dinner (6-hour), continuous glucose monitoring (CGM) metrics and early and late glucose incremental area under the curves (iAUCs) and delivered insulin doses were evaluated. The association of C/FP and HCLs with postprandial glucose and insulin patterns was analyzed by univariate analysis of variance (ANOVA) with a two-factor design. RESULTS: Postprandial glucose time-in-range 70 to 180 mg/dL was optimal after breakfast (78.3 ± 26.9%), lunch (72.7 ± 26.1%), and dinner (70.8 ± 27.3%), with no significant differences between HCLs. Independent of C/FP, late glucose-iAUC after lunch was significantly lower in C-IQ users than 670G and 780G (P < .05), with no significant differences at breakfast and dinner. Postprandial insulin pattern (Ins3-6h minus Ins0-3h) differed by type of HCLs at lunch (P = .026) and dinner (P < .001), being the early insulin dose (Ins0-3h) higher than the late dose (Ins3-6h) in 670G and 780G users with an opposite pattern in C-IQ users. CONCLUSIONS: Independent of different proportions of dietary carbohydrates, fat, and protein, postprandial glucose response was similar in users of different HCLs, although obtained through different automatic insulin delivery patterns.